Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis.

BACKGROUND: Pain management is one of the most important interventions in the emergency medical services. The femoral nerve block (FNB) is, among other things, indicated for pre- and post-operative pain management for patients with femoral fractures but its role in the pre-hospital setting has not been determined. The aim of this review was to assess the effect and safety of the FNB in comparison to other forms of analgesia (or no treatment) for managing acute lower extremity pain in adult patients in the pre-hospital setting. METHODS: A systematic review (PROSPERO registration (CRD42018114399)) was conducted. The Cochrane and GRADE methods were used to assess outcomes. Two authors independently reviewed each study for eligibility, extracted the data and performed risk of bias assessments. RESULTS: Four studies with a total of 252 patients were included. Two RCTs (114 patients) showed that FNB may reduce pain more effectively than metamizole (mean difference 32 mm on a 100 mm VAS (95% CI 24 to 40)). One RCT (48 patients) compared the FNB with lidocaine and magnesium sulphate to FNB with lidocaine alone and was only included here for information regarding adverse effects. One case series included 90 patients. Few adverse events were reported in the included studies. The certainty of evidence was very low. We found no studies comparing FNB to inhaled analgesics, opioids or ketamine. CONCLUSIONS: Evidence regarding the effectiveness and adverse effects of pre-hospital FNB is limited. Studies comparing pre-hospital FNB to inhaled analgesics, opioids or ketamine are lacking.

Intraoperative methadone for postoperative pain after laparoscopic hysterectomy: Protocol for a randomised, double-blind trial.

BACKGROUND: Hysterectomy is often carried out as same-day surgery. Treatment of postoperative pain is, therefore, of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Theoretically, a single intraoperative dose could provide long-lasting pain relief. METHODS: This is a single-centre, investigator-initiated, randomised, double-blind study. Two-hundred and fifty women, scheduled to undergo hysterectomy at Horsens Region Hospital, Denmark, are randomized to receive methadone (0.2 mg/kg) or morphine (0.2 mg/kg) intraoperatively, 60 minutes before extubation. Primary outcomes are opioid consumption at 6 and 24 hours. Secondary outcomes include pain intensity at rest and during coughing at 1, 3, 6, 24 and 48 hours; patient satisfaction at 3 and 24 hours, postoperative nausea and vomiting at 6, 24 and 72 hours, adverse events in the postanaesthesia care unit (PACU) and time until readiness for discharge. Another outcome is persistent abdominal pain after 4 months. CONCLUSIONS: The study outlined in this protocol will provide important information about the use of methadone in same-day hysterectomy patients. The results will presumably be applicable to other types of surgery involving visceral pain.

Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial.

Background: Laparoscopic hysterectomy is often carried out as day-stay surgery. Minimising postoperative pain is therefore of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Therefore, a single intraoperative dose could provide long-lasting pain relief. Methods: Patients scheduled to undergo laparoscopic hysterectomy were randomly allocated to receive methadone (0.2 mg kg-1) or morphine (0.2 mg kg-1) intraoperatively, 60 min before tracheal extubation. Primary outcomes were opioid consumption (oral morphine equivalents in milligrams) at 6 and 24 h. Secondary outcomes included pain intensity at rest and during coughing, patient satisfaction, postoperative nausea and vomiting, and adverse events up to 72 h after completion of surgery. Results: The postoperative median opioid consumption was reduced in the methadone group compared with the morphine group at 6 h (35.5 [0-61] mg vs 48 [31-74.5] mg; P=0.01) and 24 h (42 [10-67] mg vs 54.5 [31-83] mg; P=0.03). On arrival at the PACU, pain at rest was significantly lower in patients receiving methadone (numeric rating scale: 3 [2-5] vs 5 [3-6]), whereas pain scores at rest and coughing were not significantly different throughout the rest of the observation period. No differences in other secondary outcomes were found. Conclusions: In this randomised, blinded, controlled trial, opioid consumption was reduced during the first 24 postoperative hours in patients receiving methadone without causing an increase in adverse events. The difference observed might be considered as small and of limited clinical relevance. Clinical trial registration: NCT03908060; EudraCT no. 2018-004351-20.

[Intraoperative methadone for post-operative pain].

Methadone is an opioid with several desirable pharmacological features, including a long elimination half-life. Several studies have suggested that a single intraoperative dose reduces post-operative pain and opioid consumption. In this review, we summarise the current knowledge of intraoperative methadone for the treatment of post-operative pain and propose recommendations for clinical use and future research.

Prehospital intravenous fentanyl administered by ambulance personnel: a cluster-randomised comparison of two treatment protocols.

BACKGROUND: Prehospital acute pain is a frequent symptom that is often inadequately managed. The concerns of opioid induced side effects are well-founded. To ensure patient safety, ambulance personnel are therefore provided with treatment protocols with dosing restrictions, however, with the concomitant risk of insufficient pain treatment of the patients. The aim of this study was to investigate the impact of a liberal intravenous fentanyl treatment protocol on efficacy and safety measures. METHODS: A two-armed, cluster-randomised trial was conducted in the Central Denmark Region over a 1-year period. Ambulance stations (stratified according to size) were randomised to follow either a liberal treatment protocol (3 µg/kg) or a standard treatment protocol (2 µg/kg). The primary outcome was the proportion of patients with sufficient pan relief (numeric rating scale (NRS, 0-10) < 3) at hospital arrival. Secondary outcomes included abnormal vital parameters as proxy measures of safety. A multi-level mixed effect logistic regression model was applied. RESULTS: In total, 5278 patients were included. Ambulance personnel following the liberal protocol administered higher doses of fentanyl [117.7 µg (95% CI 116.7-118.6)] than ambulance personnel following the standard protocol [111.5 µg (95% CI 110.7-112.4), P = 0.0001]. The number of patient with sufficient pain relief at hospital arrival was higher in the liberal treatment group than the standard treatment group [44.0% (95% CI 41.8-46.1) vs. 37.4% (95% CI 35.2-39.6), adjusted odds ratio 1.47 (95% CI 1.17-1.84)]. The relative decrease in NRS scores during transport was less evident [adjusted odds ratio 1.18 (95% CI 0.95-1.48)]. The occurrences of abnormal vital parameters were similar in both groups. CONCLUSIONS: Liberalising an intravenous fentanyl treatment protocol applied by ambulance personnel slightly increased the number of patients with sufficient pain relief at hospital arrival without compromising patient safety. Future efforts of training ambulance personnel are needed to further improve protocol adherence and quality of treatment. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02914678 ). Date of registration: 26th September, 2016.

Acute pain in the prehospital setting: a register-based study of 41.241 patients.

BACKGROUND: Acute pain is a frequent symptom, but little is known about the frequency and causes of acute pain in the prehospital population. The objectives of this study were to investigate the frequency of moderate to severe pain among prehospital patients and the underlying causes according to primary hospital diagnose codes. METHODS: This was a register-based study on 41.241 patients transported by ambulance. Information on moderate to severe pain [Numeric Rating Scale (NRS, 0-10) > 3 or moderate pain or higher on 4-point likert scale] was extracted from a national electronic prehospital patient record. Patient information was merged with primary hospital diagnose codes based on the 10th version of the International Classification of Diseases (ICD-10) to investigate underlying causes of pain. RESULTS: 11.430 patients (27.7%) reported moderate to severe pain during ambulance transport. As a measure of opioid demanding acute pain, 3.275 of 41.241 patients (7.9%) were treated with intravenous fentanyl. Underlying causes of pain were heterogenic according to ICD-10 chapters with injuries being the largest group of patients with moderate to severe pain (XIX: 42.8% of 8.041 patients), followed by non-specific diagnoses (XVIII: 28.5% of 7.101 patients and XXI: 31.6% of 5.148 patients), diseases of the circulatory system (IX: 22.1% of 4.812 patients) and other (20.3% of 16.139 miscellaneous patients). DISCUSSION: Due to the high frequency of moderate to severe pain affecting a wide range of patients, more attention on acute pain is necessary. Whether ambulance personnel have sufficient options for treating various pain conditions might be a subject of future evaluation. Non-specific diagnoses accounted for surprisingly many patients with moderate to severe pain, of which many were treated with intravenous fentanyl. This may be substance of further investigation. CONCLUSIONS: Moderate to severe pain is a highly frequent and probably underestimated symptom among patients transported by ambulance. Underlying causes of pain are heterogenic as described by primary hospital diagnose codes. More focus on the treatment of acute pain is needed.

Prehospital triage of patients diagnosed with perforated peptic ulcer or peptic ulcer bleeding: an observational study of patients calling 1-1-2.

BACKGROUND: Triage systems are used in emergency medical services to systematically prioritize prehospital resources according to individual patient conditions. Previous studies have shown cases of preventable deaths in emergency medical services even when triage systems are used, indicating a potential undertriage among some conditions. The aim of this study was to investigate the triage level among patients diagnosed with perforated peptic ulcer (PPU) or peptic ulcer bleeding (PUB). METHODS: In a three-year period in Central Denmark Region, all patients hospitalized within 24 h after a 1-1-2 emergency call and who subsequently received either a PPU or a PUB (hereinafter combined and referred to as PPU/PUB) or a First Hour Quintet (FHQ: respiratory failure, stroke, trauma, cardiac chest pain, and cardiac arrest) diagnosis were investigated. A modified Poisson regression was used to estimate the relative risk of receiving the highest and lowest prehospital response level. Also, a linear regression analysis was used to estimate the relative risk of 30-day mortality. RESULTS: Of 8658 evaluated patients, 263 were diagnosed with PPU/PUB. After adjusting for relevant confounding variables, patients diagnosed with PPU/PUB were less likely to receive ambulance transportation compared to patients diagnosed with stroke, RR = 1.41 (CI: 1.28-1.56); trauma, RR = 1.28 (CI: 1.15-1.42); cardiac chest pain, RR = 1.47 (CI: 1.33-1.62); and cardiac arrest, RR = 1.44 (CI: 1.31-1.42). Among patients diagnosed with PPU/PUB, 6.5% (CI: 3.3-9.7) did not receive ambulance transportation. The proportion of patients not receiving ambulance transportation was higher among patients diagnosed with PPU/PUB compared to patients diagnosed with an FHQ diagnosis. The 30-day mortality rate among patients diagnosed with PPU/PUB was 7.8% (CI: 4.2-11.1). This was lower than the 30-day mortality rate among patients diagnosed with respiratory failure (P = 0.010), stroke (P = 0.001), and cardiac arrest (P < 0.001), but comparable to the 30-day mortality among patients diagnosed with cardiac chest pain (P = 0.080) and trauma (P = 0.281). CONCLUSION: Among patients calling 1-1-2, fewer patients diagnosed with PPU/PUB received ambulance transportation than patients diagnosed with FHQ diagnoses, despite a high mortality among patients diagnosed with PPU/PUB.

Prehospital triage of patients suffering severe dyspnoea using N-terminal pro-brain natriuretic peptide, the PreBNP trial: a randomised controlled clinical trial.

PURPOSE: The purpose of this study was to examine whether the addition of brain natriuretic peptide measurement to the routine diagnostic work-up by prehospital critical care team physicians improves triage in patients with severe dyspnoea. METHODS: Prehospital critical care team physicians randomly assigned patients older than 18 years with severe dyspnoea to routine diagnostic work-up or diagnostic work-up with incorporated point-of-care N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement. The primary endpoint was the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology. RESULTS: A total of 747 patients were randomly assigned and 711 patients consented to participate, 350 were randomly assigned to the NT-proBNP group and 361 to the routine work-up group. NT-proBNP was measured in 90% (315/350) of patients in the NT-proBNP group and in 19% (70/361) of patients in the routine work-up group. There was no difference in the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology between the NT-proBNP group and the routine work-up group (75% vs. 69%, P=0.22) in the intention-to-treat analysis. Sensitivity analysis according to the de facto diagnostics performed showed results consistent with this. No differences in hospital length of stay, intensive care unit admission rates or mortality between the NT-proBNP group and the routine work-up group were observed. CONCLUSION: Routine supplementary point-of-care measurement of NT-proBNP in patients with severe dyspnoea did not improve triage of patients with dyspnoea primarily caused by heart disease. ClinicalTrials.gov identifier NCT02050282.

Prehospital intravenous fentanyl to patients with hip fracture: an observational cohort study of risk factors for analgesic non-treatment.

BACKGROUND: Patients with proximal femoral neck fracture have a high short-term mortality, a high risk of postoperative complications, and impaired quality of life. One of the challenges related to the prehospital treatment of these patients is to administer systemic opioids fast and properly. Effective analgesic prehospital treatment ought be initiated rapidly in order to alleviate the stress that follows acute pain, to facilitate transportation, and to improve quality of care. The objectives of this study were to explore the prevalence of prehospital administration of intravenous fentanyl to patients with proximal femoral neck fracture in the ambulances and to assess risk factors for analgesic non-treatment. METHODS: This was a register-based observational cohort study of patients with proximal femoral neck fracture from the North Denmark Region transported by ambulance. The patients were identified via the Danish Interdisciplinary Hip Fracture Registry over a 3-year period from 1 July 2011 to 30 June 2014. This hospital registry contains data on several patient characteristics used for the risk factor analysis. Data on prehospital treatment (intravenous fentanyl) and patient monitoring were registered in an electronic prehospital patient record. A modified Poisson regression with robust standard errors was carried out with intravenous fentanyl as the primary binary outcome and the following explanatory variables: age, sex, Charlson Comorbidity Index score, housing, body mass index, type of fracture, fracture displacement, prior consultation with general practitioner, dispatch triage level, and time with ambulance personnel. RESULTS: In total, 2,140 patients with proximal femoral neck fracture were transported by ambulance, of which 584 (27.3%, 95% CI: 25.4-29.2) were treated with intravenous fentanyl. Risk factors for non-treatment were: older age, male sex (RR 0.77, 95% CI: 0.64-0.91), institutional housing (RR 0.72, 95% CI: 0.56-0.92), medial fracture (RR 0.74, 95% CI: 0.60-0.92), short time with ambulance personnel, Charlson Comorbidity Index score > 1, year of fracture (2011), low levels of urgency at dispatch, and if seen by general practitioners prior to transport. DISCUSSION: Education of ambulance personnel in assessing and treating patients with hip fracture seems to be required. Also, future studies should consider alternative or supportive pain treatment options with suitable analgesic effects and side effects. CONCLUSIONS: Few patients with proximal femoral neck fracture were treated with intravenous fentanyl, and several risk factors were associated with prehospital analgesic non-treatment. Future prospective studies should explore covariates of socioeconomic, cultural, and psychological origin to provide further insight into the multifactorial causes of non-treatment of acute pain.